Eli Lilly’s logo appears at the company’s office in San Diego, California, USA on November 21, 2025.
Mike Blake | Reuters
Eli Lilly announced Thursday that its next-generation obesity drug, retatrutide, has passed its first late-stage trial in type 2 diabetes patients, helping them control their blood sugar levels and lose weight.
The drug lowered hemoglobin A1c – an important measure of blood sugar levels – by an average of 1.7% to 2% compared to placebo across different dosages after 40 weeks, meeting the study’s main goal. Patients began the study with HbA1c levels ranging from 7% to 9.5% and were not taking other diabetes medications.
Retatrutide also met the study’s second goal, helping patients on the highest dose lose an average of 16.8% of their weight, or 36.6 pounds, after 40 weeks, studying only patients who continued to take the drug. When all participants were analyzed, including those who stopped treatment, the highest dose of the drug helped patients lose 15.3% of their weight.
Patients with type 2 diabetes have historically had difficulty losing weight, so Lilly is “very excited” that the drug has resulted in both competitive drops in blood sugar levels and significant weight loss, Ken Custer, president of Lilly Cardiometabolic Health, said in an interview.
The company is also “very pleased” with the relatively low discontinuation rate due to side effects, which is as high as 5%, he added.
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These are the second late-stage results so far on retatruide, which works differently than existing injections and appears to be more effective, at least for weight loss. Lilly is betting big on retatrutide as the next leg of its obesity portfolio after its blockbuster weight-loss injectable Zepbound and its upcoming pill Orforglipron.
But Lilly has not yet filed for approval of the drug for obesity or diabetes. The company expects to announce results from seven additional Phase III trials of the drug by the end of the year.
There are no comparative studies between retatruide and other medicines, making it difficult to directly compare effectiveness.
Still, retatruide’s A1C reduction doesn’t appear to be the largest Lilly has seen in its portfolio: The highest dose of Zepbound lowered the measure by more than 2% after 40 weeks in two separate studies in diabetes patients.
However, Custer said the A1C reduction from retatruide was still “very, very strong” compared to other diabetes drugs that don’t target gut hormones.
He also said it will be important to have options in the area of obesity and diabetes because “not everyone can be helped or satisfied with the same treatment.” The decision about which drug to take will depend on “customization of solutions and patients,” particularly at the beginning of their diabetes treatment, he added.
For example, Custer said patients who want to regulate their blood sugar may benefit from either Zepbound or retatruide. But if they want to lose more weight, the latter might be a better option, he said.
In the two separate diabetes studies, Zepbound helped patients lose slightly less weight than retatruide. In a study called SURPASS-2, the highest dose of Zepbound helped patients lose an average of 13.1% of their weight after 40 weeks. In the other study, SURPASS-1, the highest dose helped patients lose an average of 11% of their weight after 40 weeks.
The safety profile of retatrutide was similar to that of other injectable medications for diabetes and obesity, causing primarily gastrointestinal side effects. Approximately 26.5% of patients receiving the highest dose experienced nausea, while approximately 22.8% and 17.6% experienced diarrhea and vomiting, respectively.
Only a few patients suffered from dysesthesia, an unpleasant nerve sensation.
Retatrutide is called a “triple-G” drug and mimics three hunger-regulating hormones – GLP-1, GIP and glucagon – rather than just one or two like existing treatments. This appears to have a stronger effect on a person’s appetite and satisfaction with food than other treatments.
Tirzepatide, the active ingredient in Zepbound, mimics GLP-1 and GIP. Novo Nordisk’s semaglutide, the active ingredient in Wegovy, only mimics GLP-1.
As Retatrutide gets closer to market, Novo is trying to catch up with Lilly. In March 2025, Novo said it had agreed to pay up to $2 billion for the rights to an early experimental drug from Chinese pharmaceutical company United Laboratories International.
Novo’s newly acquired drug is a clear potential competitor to retatrutide because it also takes a three-pronged approach to promoting weight loss and regulating blood sugar. However, Novo’s treatment is much earlier in development, meaning it will take several years to reach patients.
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